The immune mechanism by which the hamster acquires resistance to infection with Treponema pertenue, the causative agent of frambesia or yaws, has not been elucidated. Serum or cells (spleen or lymph node) obtained from hamsters resistant to frambesial infection were transferred to normal syngeneic recipients, who were subsequently infected with T. pertenue. The following parameters were used to measure the ability of immune serum or cells to confer resistance on recipient hamsters to frambesial infection: inhibiton of the development of cutaneous lesions, decreased weight and number of treponemes in the inguinal lymph nodes. This investigation demonstrated that immune serum conferred protection on recipient hamsters infected with T. pertenue. Discontinuation of the administration of immune serum (18 days after frambesial infection) did not result in the development of cutaneous lesion. Since the inguinal lymph nodes contained a sizeable number of treponemes (2.6 x 10 to the 5th power), immune serum failed to prevent frambesial infection. Recipients of immune spleen or lymph node cells initially developed frambesial lesions nine days after infection. The frambesial lesions began to resolve 12-14 days after infection and by day 21 had completely regressed. These results illustrated that humoral factors and cells are involved in resistance of the hamster to frambesial infection. Experimental frambesial infection of the hamster might be an alternative model to elucidate the immune response mechanism by which man recovers from treponemal and more specifically syphilitic infection.